Diagnostic, Therapeutic, and Theranostic Multifunctional Microneedles.

Microneedles (MNs) have maintained their popularity in therapeutic and diagnostic medical applications throughout the past decade. MNs are originally designed to gently puncture the stratum corneum layer of the skin and have lately evolved into intelligent devices with functions including bodily fluid extraction, biosensing, and drug administration. MNs offer limited invasiveness, ease of application, and minimal discomfort. Initially manufactured solely from metals, MNs are now available in polymer-based varieties. MNs can be used to create systems that deliver drugs and chemicals uniformly, collect bodily fluids, and are stimulus-sensitive. Although these advancements are favorable in terms of biocompatibility and production costs, they are insufficient for the therapeutic use of MNs. This is the first comprehensive review that discusses individual MN functions toward the evolution and development of smart and multifunctional MNs for a variety of novel and impactful future applications. The study examines fabrication techniques, application purposes, and experimental details of MN constructs that perform multiple functions concurrently, including sensing, drug-molecule release, sampling, and remote communication capabilities. It is highly likely that in the near future, MN-based smart devices will be a useful and important component of standard medical practice for different applications.

New cyclometalated iridium(III) complexes bearing substituted 2-(1H-benzimidazol-2-yl)quinoline: Synthesis, characterization, electrochemical and anticancer studies.

New iridium(III) compounds (C1-C3) bearing 2-(1H-benzimidazol-2-yl)quinoline ligands with different side groups (benzyl, 2,3,4,5,6-pentamethylbenzyl and 2,3,4,5,6-pentafluorobenzyl) were synthesized and characterized by using spectroscopic analyses. The effects of different side groups of iridium compounds on the photophysical and electrochemical properties have been investigated. The cytotoxicity and apoptosis of the compounds have been evaluated on breast cancer cell lines using various methods including MTT assay, flow cytometry, qRT-PCR, and colony formation. The cytotoxicity of C1, expressed as IC50 values, was found to be 11.76 µM for MDA-MB-231 and 5.35 µM for MCF-7 cells. For C3, the IC50 value was 16.22 µM for MDA-MB-231 and 8.85 µM for MCF-7 cells. In both cell lines, increased levels of Bax and caspase 3, along with downregulation of BCL-2 and positive annexin V staining, were observed, confirming apoptosis. Moreover, the colony-forming abilities in both cell lines decreased after C1 and C3 complex treatment. All these results suggest that the compounds C1 and C3 may have potential in the treatment of breast cancer, though further research is needed to confirm their efficacy.

Direct embryonic biopsy with transcervical embryoscopy is an effective method for karyotyping and morphology assessment in miscarriages.

PURPOSE: The main purpose of this study is to compare the validity of transcervical embryoscopy method with standard uterine evacuation method in detecting more accurate karyotypes in miscarriages below tenth week of pregnancy. Additionally, the frequency and distribution of fetal morphological abnormality were evaluated. METHODS: A prospective study was carried out at the Gazi University Faculty of Medicine, Department of Obstetrics and Gynecology. Patients with missed abortions between sixth and tenth gestational weeks were included in the study group, and fetal morphological examination and direct embryonic biopsy were performed by transcervical embryoscopy. The control group consisted of patients who experienced miscarriage and genetic material obtained from routine uterine evacuation between February and October 2023. RESULT: A total of 60 patients in the study group and 189 patients in the control group were evaluated. The median ages, previous miscarriage numbers, median gravida numbers, and median gestational weeks were comparable between groups. Chromosomal abnormality was detected in 24 (42.8%) and 52 embryos (29.9%) in the study and control groups, respectively (p = 0.004). Culture failure rates were 6.6% (n = 4) and 7.9% (n = 15) in the study and control groups, respectively. In the study group, 12 embryos had a morphological abnormality in which 6 of them had normal karyotype. CONCLUSION: Direct embryonic biopsy with transcervical embryoscopy is an effective method to exclude maternal decidual cell contamination and placental mosaicism in miscarriages for karyotype analysis. In addition, detecting anomalies in morphology might contribute our understanding in the process of miscarriages which arises independent from structural/numerical chromosomal abnormalities.

Use of serum copper and zinc levels in the diagnostic evaluation of endometrioma and epithelial ovarian carcinoma.

OBJECTIVE: The aim of this study is to evaluate serum copper (Cu) and zinc (Zn) levels in patients with epithelial ovarian cancer and endometrioma. MATERIALS AND METHODS: We included 21 epithelial ovarian cancer patients, 47 endometrioma patients, 31 healthy women of reproductive age, and 10 healthy women in menopause. Cu and Zn levels and Cu/Zn ratios were compared. RESULTS: In the endometrioma group, Cu levels (P = 0.04) and Cu/Zn ratio (P < 0.01) were higher, while Zn levels (P < 0.01) were lower compared to the control group. The threshold value of 1.15 with 62% sensitivity and 61% specificity was calculated for the Cu/Zn ratio using the ROC curve (AUC = 0.688; P = 0.005). In the ovarian cancer group, Cu levels (P ≤ 0.01) and Cu/Zn ratio (P = 0.02) were higher, whereas Zn levels (P ≤ 0.02) were lower compared to the control group. The Cu/Zn ratio threshold value of 1.37 was calculated with 76% sensitivity and 90% specificity (AUC = 0.829; P = 0.004). The Zn level was lower (P = 0.02), and the Cu/Zn ratio was higher (P = 0.01) in the ovarian cancer group compared to the endometrioma group. CONCLUSION: The threshold value of the Cu/Zn ratio for ovarian cancer could be determined with a specificity of 90%, whereas the sensitivity and specificity of the Cu/Zn ratio for endometrioma were low.

Dual trigger with the combination of gonadotropin-releasing hormone agonist and standard dose of human chorionic gonadotropin improves in vitro fertilisation outcomes in poor ovarian responders.

The study aimed to evaluate the impact of the dual trigger with the combination of GnRH agonist and standard dose of recombinant hCG on IVF outcomes in poor ovarian responders with GnRH antagonist protocol. 1283 cycles of 1010 poor responder patients according to Bologna criteria were retrospectively analysed in terms of final oocyte maturation: dual trigger group (250 µg hCG + 0.2 mg triptorelin) or standard group (250 µg hCG). Primary outcome measures were the number of retrieved and mature oocytes. The secondary outcome measures were clinical pregnancy rates and live birth rates.The number of retrieved oocytes, mature oocytes, and the top-quality embryos transferred were significantly higher in the dual trigger group (p < .001). Fertilisation rates (73.6% vs 69.6%, p = .009), implantation rates (18.7% vs 14.6, p = .039), clinical pregnancy rate per embryo transfer (27.5% vs. 19.9%, p = .010) and live birth rate per embryo transfer (21.6% vs. 14.9%, p = .011) were also significantly higher in the dual trigger group as compared to the hCG trigger group. The usage of dual trigger with a GnRH agonist and a standard dosage of hCG could improve clinical pregnancy rates and live birth rates in poor ovarian responders undergoing GnRH antagonist IVF/ICSI cycles.IMPACT STATEMENTWhat is already known on this subject? Dual trigger with standard dose of hCG has been the subject of trials in normal responders to optimise IVF outcomes. The results of these studies showed significant improvements in implantation and pregnancy rates with an increase in the number of mature oocytes retrieved. As a result, dual trigger has become a popular ovulation trigger option in GnRH antagonist cycles.What do the results of this study add? There is limited data about the use of dual trigger in poor ovarian responders (PORs). According to our study, increasing the number of retrieved oocytes, mature oocytes, the number of fertilised oocytes, the number of transferred embryos and top quality embryos transferred by using dual trigger in patients with PORs have a positive impact on pregnancy outcomes.What are the implications of these findings for clinical practice and/or further research? These findings implies potential advantages of dual trigger usage for improving IVF outcomes in PORs. With large sample sized prospective randomised trials, dual trigger with combination of GnRHa and a standard dose of hCG might replace the traditional ovulation trigger with hCG in PORs.

Subsequent IVF outcomes following antibiotic therapy for chronic endometritis in patients with recurrent implantation failure.

AIM: The aim is to identify the chronic endometritis (CE) incidence in recurrent implantation failure (RIF) patients undergoing in vitro fertilization (IVF) treatment and compare the IVF outcomes of RIF patients with CE following antibiotic therapy with RIF patients without CE. Another purpose is to compare the IVF outcomes of described RIF patients with patients undergoing the first cycle of IVF. METHODS: In this retrospective cohort study, CE was diagnosed with CD-138 immunohistochemical staining. Among RIF patients, two groups were formed as group 1, including patients diagnosed with CE and treated by antibiotics (n = 129), and group 2, including patients without CE (n = 103). Patients with the first IVF cycle having similar infertility etiologies with RIF patients were reviewed as group 3 (n = 932). RESULTS: CE was diagnosed in 55.6% of RIF patients. The number of oocytes retrieved was not different between groups. Implantation rates (IR) were similar after antibiotic treatment in RIF patients with or without CE. However, Group 3 had a higher IR (41.1%) than group 1 and 2 (23.1% and 30.1%, respectively) (p < 0.001). Clinical pregnancy (CPR) and live birth rates (LBR) were comparable between RIF groups. However, CPR and LBR were significantly higher in group 3 (48.6% and 40.5%) than group 1 (36.4% and 27.9%), and group 2 (37.9% and 30.1%) (p = 0.007 and p = 0.005, respectively). CONCLUSION: Unidentified endometrial factors except CE may also affect the implantation process, although CE is a frequent finding in patients with RIF. Reproductive outcomes may not be improved only with antibiotics in RIF patients with CE.

Comparison of frozen-thawed embryo transfer protocols in patients with previous cycle cancellation due to uterine peristalsis: a pilot study

Background/aim: To investigate the optimal protocol for frozen-thawed embryo transfer (FET) cycles in patients who previously had a cycle cancellation due to uterine peristalsis (UP). Materials and methods: Thirty-four patients with previous embryo transfer (ET) cancellation due to UP during artificial cycle (AC) were included retrospectively. In the proceeding cycle, endometrium was prepared with AC (n: 23) in AC-FET group or with stimulated cycle that contains letrozole (L) (n: 11) in L-FET group. Intravenous bolus dose of 6.75 mg atosiban (Tractocile; Ferring Pharmaceuticals, Switzerland) injection was performed to all patients of AC-FET group due to UP ≥ 4/min on the planned ET day of proceeding cycle. Atosiban was not used in L-FET group. Primary outcome was live birth rate (LBR) per ET. Secondary outcomes were clinical pregnancy rate (CPR) per ET, implantation rate (IR), cycle cancellation rate. Results: The baseline characteristics such as age, body mass index, antral follicle count, duration of infertility, and the number of prior in vitro fertilization attempts of each group were similar. The IR, CPR per ET, LBR per ET, CPR per cycle and LBR per cycle were significantly higher; cycle cancellation rates were significantly lower in L-FET group as compared to the AC-FET group. Conclusion: Endometrial preparation with letrozole significantly improves CPR and LBR in FET cycles of patients with previous cycle cancellations due to UP.

Advances in Controlled Oxygen Generating Biomaterials for Tissue Engineering and Regenerative Therapy.

Oxygen (O2) generating biomaterials are emerging as important compositions to improve our capabilities in supporting tissue engineering and regenerative therapeutics. Several in vitro studies demonstrated the usefulness of O2 releasing biomaterials in enhancing cell survival and differentiation. However, more efforts are needed to develop materials that can provide sustained O2 release for the long-term. In this paper, we present different O2 generating sources, including hydrogen peroxide, sodium percarbonate, calcium peroxide and magnesium peroxide, and also cover types of carriers and relevant methods of fabricating O2 generating systems. Then, the applications of O2 generating materials in supporting engineered constructs, supplying high O2 demanding cell transplants, and supporting ischemic tissues are discussed. Moreover, the challenges and future perspectives are highlighted.

Impact of the sexual abstinence period on the production of seminal reactive oxygen species in patients undergoing intrauterine insemination: A randomized trial.

AIM: To evaluate whether the duration of sexual abstinence has impact on oxidative stress in semen samples. METHODS: Oxidative reaction was tested for different levels of reactive oxygen species (ROS) by nitro blue tetrazolium assay in 90 patients with the diagnosis of unexplained or male factor infertility that were grouped into 3 groups as 0-2 (group 1), 3-4 (group 2) and >4 days (group 3) of duration of sexual abstinence. Subsequently, the remaining semen was prepared by gradient method for ovarian stimulation and intrauterine insemination (IUI) cycles to compare pregnancy rates in terms of different levels of ROS and different abstinence periods. RESULTS: Increased staining pigment intensity was related to higher level of ROS in >4 days' group as compared to groups 0-2 and 3-4 days (70% vs 43.3% and 50%, P = 0.013 and P = 0.014, respectively). Pregnancy rates significantly decrease with prolonged abstinence period (26.7%, 16.7% and 6.7% in groups 1, 2 and 3, respectively, P = 0.039). Progressive motile sperm count after gradient method of sperm preparation for IUI was highest in 3-4 days of abstinence period than shorter and longer abstinence groups. CONCLUSION: Longer duration of sexual abstinence causes higher oxidative stress and decreases pregnancy rates in IUI cycles.

Prisoners seeking healthcare in emergency department.

OBJECTIVE: To evaluate inmate referrals to emergency department of a tertiary healthcare facility in terms of demographical and clinical characteristics as well as their impact on the department. METHODS: The retrospective cross-sectional study was conducted at Ankara Numune Training and Research Hospital, Ankara, Turkey and comprised data of incarcerated patients who were brought to the emergency department from January 01, 2010, to December 31, 2012. Demographical characteristics, consultations, duration of hospitalisation, recurrent admissions, disposal and mortality rates were noted. The referrals were grouped as surgical conditions, medical disorders, Eye, Ear, Nose, Throat problems, injury and psychiatric disorders. The groups were then subdivided according to diagnosis. SPSS 22 was used for data analysis. RESULTS: Of the 856 patients, 804(93.4%) were men and 52(6.1%) were women. The overall mean age was 37.54±14.81 years (range: 15-83 years). The number of patients was the highest in the medical group 363(42.4%) and the lowest in the Eye, Ear, Nose, Throat group 56(6.5%). Mean age of the surgical group was significantly lower than the medical group (p<0.001) but significantly higher than that of the trauma group (p=0.001). CONCLUSIONS: Functional emergency response units, strict emergency triage of inmates and their rapid care and management in jails can help avoid referring these patients to already overcrowded emergency departments.

The effect of swim-up and gradient sperm preparation techniques on deoxyribonucleic acid (DNA) fragmentation in subfertile patients.

PURPOSE: To compare the effect of two different sperm preparation techniques, including swim-up and gradient methods on sperm deoxyribonucleic acid (DNA) fragmentation status of semen samples from unexplained and mild male factor subfertile patients undergoing intrauterine insemination (IUI). DESIGN: A prospective randomized study was conducted in 65 subfertile patients, including 34 unexplained and 31 male factor infertility to compare basal and post-procedure DNA fragmentation rates in swim-up and gradient techniques. Sperm DNA fragmentation rates were evaluated by a sperm chromatin dispersion (SCD) test in two portions of each sample of semen that was prepared with either swim-up or gradient techniques. Sperm motility and morphology were also assessed based on WHO 2010 criteria. RESULTS: Swim-up but not gradient method yielded a statistically significant reduction in the DNA fragmented sperm rate after preparation as compared to basal rates, in the semen samples of both unexplained (41.85 ± 22.04 vs. 28.58 ± 21.93, p < 0.001 for swim-up; and 41.85 ± 22.04 vs. 38.79 ± 22.30, p = 0.160 for gradient) and mild male factor (46.61 ± 19.38 vs. 30.32 ± 18.20, p < 0.001 for swim-up and 46.61 ± 19.38 vs. 44.03 ± 20.87, p = 0.470 for gradient) subgroups. CONCLUSIONS: Swim-up method significantly reduces sperm DNA fragmentation rates and may have some prognostic value on intrauterine insemination in patients with decreased sperm DNA integrity.

Two cases of first onset intrahepatic cholestasis of pregnancy associated with moderate ovarian hyperstimulation syndrome after IVF treatment and review of the literature.

Intrahepatic cholestasis of pregnancy (ICP) is an uncommon disorder, which generally occurs in the second and third trimester of pregnancy with symptoms of pruritus. The cause of ICP is unknown but genetic, hormonal and environmental factors contribute to its pathogenesis. The aetiology of ICP is unclear but elevation in oestrogen levels thought to cause ICP is typically seen in the third trimester of pregnancy, and for this reason it is not usually considered in the differential diagnosis of pruritus and liver function disorders in the first trimester of the pregnancy. We present two cases of pregnancy after IVF treatment diagnosed with ICP following the development of OHSS, deteriorating liver function tests and severe pruritus.

Luteal phase support in intrauterine insemination cycles: a prospective randomized study of 300 mg versus 600 mg intravaginal progesterone tablet.

Vaginal progesterone (P) has been suggested to be used for luteal phase support (LPS) in controlled ovarian stimulation (COH)-intrauterine insemination (IUI) cycles, however, no concensus exists about the best P dose. Therefore, considering the fecundability rate as the primary end point, our main objective was to find the optimal dose of P in COH-IUI cycles, comparing the two groups of women, each of which comprised of 100 women either on 300 mg or 600 mg of intravaginal P tablets, in a prospective randomized study design. The mean age of the women, duration of infertility, basal and day of hCG injection hormone levels in the female and sperm parameters were similar in the two study groups. Also, duration and dose of gonadotropin given, number of follicles, endometrial thickness, the total, ongoing and multiple pregnancy rates were comparable in both groups. We, therefore, claim that 300 mg of intravaginal micronized P should be the maximum dose of LPS in IUI cycles.

Advanced oxidation protein products and malondialdehyde - the new biological markers of oxidative stress - are elevated in postmenopausal women.

OBJECTIVES: The aim of the study was to measure advanced oxidation protein products (AOPPs) as markers for oxidative stress to evaluate cardiovascular risk in pre- and postmenopausal women and to compare the results with malondialde-hyde (MDA) levels. MATERIAL AND METHODS: Twenty premenopausal women and 84 naturally postmenopausal patients were enrolled in the study. AOPP and MDA plasma levels were measured. The postmenopausal group was further subdivided into two groups: postmenopausal age of 40-49 and of 50-59 years. AOPP and MDA levels were compared between premenopausal, 40-49 and 50-59 year old menopausal women. RESULTS: Plasma AOPP and MDA levels in postmenopausal women were increased when compared with their premeno-pausal peers (123.83 ± 55.51 µmol/L vs. 61.59 ± 16.42 µmol/L and 6.50 ± 1.05 µmol/L vs. 5.98 ± 0.77 µmol/L; respectively). Mean plasma AOPP levels in the two menopausal age groups were both significantly higher from the premenopausal group (118.64 ± 59.1 µmol/L vs. 61.59 ± 16.42 µmol/L and 132.31 ± 48.97 µmol/L vs. 61.59 ± 16.42 µmol/L; respectively). No significant difference was found in mean AOPP levels between postmenopausal subjects of 40-49 and 50-59 years age (118.64 ± 59.12 µmol/L vs. 132.31 ± 48.97 µmol/L). Mean plasma MDA levels of each of two postmenopausal age groups were both significantly higher from the premenopausal group (6.50 ± 1.04 µmol/L vs. 5.98 ± 0.77 µmol/L and 6.50 ± 1.10 µmol/L vs. 5.98 ± 0.77 µmol/L; respectively). However, no statistically significant difference between the two postmenopausal age groups (6.50 ± 1.04 µmol/L vs. 6.50 ± 1.10 µmol/L) was found. CONCLUSIONS: AOPP and MDA levels are elevated in postmenopausal women as compared to their premenopausal peers, suggesting they can be used as markers for cardiovascular risk in postmenopausal women.

The Avaibility of Strain Elastography in a Hydatid Cyst - Interobserver Study.

BACKGROUND: To differentiate the hydatid cyst (HC) types by ultrasound elastography using two different sizes (4 mm and 8 mm) of the region of interest (ROI) and asking two different radiologists (interobserver) for their opinion. MATERIAL/METHODS: Patients with HC were evaluated by USG elastography. The statistical anayses were performed using Strain index (SI) which is the unit of strain elastography. RESULTS: A total of 26 out of 33 patients were female, and 7 were male. The mean age was 38.85±17.62 (range from 10 to 72 years). Type I: 6, Type 2: 6, Type III: 6, Type IV: 11, Type V: 4. There was no significant difference in HC SI (regardless of types) between O1 and O2, and 4-mm and 8-mm ROI (p>0.05). There was no statistically significant difference between SI of HC types of interobservers (O1-O2) and ROI sizes (4-8 mm) (p>0.05 for all parameters). The highest correlation between HC types and ROI sizes was in ROI size of 4 mm. CONCLUSIONS: The correlation between SI and types was reliable in standard-applied 4-mm ROI. There was no statistically significant difference between interobservers in SI values. Thus, elastography tecnhnique is objective for HC but not appropriate to differentiate the types.

A potential novel treatment strategy: inhibition of angiogenesis and inflammation by resveratrol for regression of endometriosis in an experimental rat model.

The aim of our study was to evaluate the effectiveness of resveratrol in experimentally induced endometrial implants in rats through inhibiting angiogenesis and inflammation. Endometrial implants were surgically induced in 24 female Wistar-Albino rats in the first surgery. After confirmation of endometriotic foci in the second surgery, the rats were divided into resveratrol (seven rats), leuprolide acetate (eight rats), and control (seven rats) groups and medicated for 21 d. In the third surgery, the measurements of mean areas and histopathological analysis of endometriotic lesions, VEGF, and MCP-1 measurements in blood and peritoneal fluid samples, and immunohistochemical staining were evaluated. After treatment, significant reductions in mean areas of implants (p < 0.01) and decreased mean histopathological scores of the implants (p < 0.05), mean VEGF-staining scores of endometriotic implants (p = 0.01), and peritoneal fluid levels of VEGF and MCP-1 (p < 0.01, for VEGF and p < 0.01, for MCP-1) were found in the resveratrol and leuprolide acetate groups. Serum VEGF (p = 0.05) and MCP-1 (p = 0.01) levels after treatment were also significantly lower in the resveratrol and leuprolide acetate groups. Resveratrol appears to be a potential novel therapeutic agent in the treatment of endometriosis through inhibiting angiogenesis and inflammation. Further studies are needed to determine the optimum effective dose in humans and to evaluate other effects on reproductive physiology.

Farmedial versus anteromedial portal drilling of the femoral tunnel in ACL reconstruction: a computed tomography analysis.

INTRODUCTION: The success of ACL reconstruction is predicated on a variety of factors. Tunnel placement plays one of the most significant roles in achieving knee kinematics and function. The purposes of this study were to compare femoral tunnel position, angle, length and posterior wall blow-out after ACL reconstruction with hamstring tendons autograft through either a farmedial portal or an anteromedial portal technique. MATERIALS AND METHODS: We evaluated 36 patients who underwent ACL reconstruction between January 2014 and July 2014 in our institute, in a prospective, randomised cohort study. All the surgical procedures were performed by a sports fellowship-trained orthopaedic surgeon with experience in both portal reaming. The operated knees were evaluated with 0.5 mm fine CT scans of 3-D CT between days 3 and 5 postoperatively. RESULTS: According to the 3-D CT measurements, the mean femoral tunnel length was significantly longer (p < 0.05) in the FAM group compared with the AM group. The femoral bone tunnel length averaged 34.2 ± 3.6 mm versus 36.6 ± 3.0 mm (p = 0.042) in AM and the FAM groups, respectively. The femoral tunnel position, as evaluated with use of the quadrant method, was more anterior in the FAM transportal technique group, and the difference between the two groups was significant (p < 0.05). CONCLUSION: FAM tranportal drilling of the femoral tunnel creates longer and anterior femoral tunnels with regard to the AM portal drilling techniques. Additional studies with clinical outcomes are required for the clinical relevance of these techniques and to show which one is superior. LEVEL OF EVIDENCE: Level I, prospective randomised comparative cohort study.

Follicle-stimulating hormone receptor (FSHR) alternative skipping of exon 2 or 3 affects ovarian response to FSH.

Genes critical for fertility are highly conserved in mammals. Interspecies DNA sequence variation, resulting in amino acid substitutions and post-transcriptional modifications, including alternative splicing, are a result of evolution and speciation. The mammalian follicle-stimulating hormone receptor (FSHR) gene encodes distinct species-specific forms by alternative splicing. Skipping of exon 2 of the human FSHR was reported in women of North American origin and correlated with low response to ovarian stimulation with exogenous follicle-stimulating hormone (FSH). To determine whether this variant correlated with low response in women of different genetic backgrounds, we performed a blinded retrospective observational study in a Turkish cohort. Ovarian response was determined as low, intermediate or high according to retrieved oocyte numbers after classifying patients in four age groups (<35, 35-37, 38-40, >40). Cumulus cells collected from 96 women undergoing IVF/ICSI following controlled ovarian hyperstimulation revealed four alternatively spliced FSHR products in seven patients (8%): exon 2 deletion in four patients; exon 3 and exons 2 + 3 deletion in one patient each, and a retention of an intron 1 fragment in one patient. In all others (92%) splicing was intact. Alternative skipping of exons 2, 3 or 2 + 3 were exclusive to low responders and was independent of the use of agonist or antagonist. Interestingly, skipping of exon 3 occurs naturally in the ovaries of domestic cats--a good comparative model for human fertility. We tested the signaling potential of human and cat variants after transfection in HEK293 cells and FSH stimulation. None of the splicing variants initiated cAMP signaling despite high FSH doses, unlike full-length proteins. These data substantiate the occurrence of FSHR exon skipping in a subgroup of low responders and suggest that species-specific regulation of FSHR splicing plays diverse roles in mammalian ovarian function.

Luteal phase support with estrogen in addition to progesterone increases pregnancy rates in in vitro fertilization cycles with poor response to gonadotropins.

In this study, our objective was to determine the effect of adding estradiol hemihydrate (E2) to progestin (P) for luteal phase support on pregnancy outcome in in vitro fertilization (IVF) cycles with poor response to gonadotropins. Ninety-five women with poor ovarian response who underwent controlled ovarian hyperstimulation (COH) with gonadotropin releasing hormone (GnRH) agonist or GnRH antagonist plus gonadotropin protocol for IVF were prospectively randomized into three groups of luteal phase support after oocyte retrieval. Group 1 (n = 33) received only intravaginal progesterone gel (Crinone 8% gel). Group 2 (n = 27) and Group 3 (n = 35) received intravaginal progesterone plus oral 2 and 6 mg estradiol hemihydrate, respectively. Main outcome measures were overall and clinical pregnancy rates (PRs) per patient. Serum LH, E2 and P levels at 7th and 14th days of luteal phase were also measured. Overall and clinical PRs were significantly higher in 2 mg E2 + P than P-only group (44% versus 18% and 37% versus 12.1%, respectively). There were no statistically significant differences between 6 mg E2 + P versus P-only and 2 mg E2 + P versus 6 mg E2 + P groups regarding PRs. Addition of 2 mg/day E2 in addition to P for luteal support significantly increase overall and clinical PRs in cycles with poor response to gonadotropins after IVF.

Effect of luteal phase support after ovulation induction and intrauterine insemination.

OBJECTIVE: This study aimed to evaluate the effect of luteal phase support on clinical pregnancy and live birth rates after ovulation induction and intrauterine insemination (IUI). METHODS: 579 cycles from 2010 to 2013 were retrospectively evaluated. Ovarian stimulation was performed with gonadotropins, and rHCG was used for ovulation triggering. All patients received IUI. 451 cycles were supported by receiving vaginal micronized progesterone capsules (142 cycles) or vaginal progesterone gel (309 cycles) whereas 128 cycles were not supported. RESULTS: Clinical pregnancy (20.6 versus 9.4%; p = 0.004) and live birth rates (14 versus 7%; p = 0.036) were higher for supported group than for unsupported group. Progesterone gel and micronized progesterone subgroups achieved similar clinical pregnancy and live birth rates (21.4 versus 19%, p = 0.567 and 14.2 versus 13.4%, p = 0.807; respectively). CONCLUSIONS: Luteal phase support improved the success of IUI cycles affecting both clinical pregnancy and live birth rates when gonadotropins were used for ovulation induction. The use of vaginal progesterone gel or micronized progesterone significantly improves clinical pregnancy rates. The live birth rates were higher in the progesterone gel group, but were similar in the micronized progesterone group compared to the unsupported group.